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Case Analysis : Stem Cell Therapy for Diabetes

Drs. Wang Xiaojuan, Wu Like and Xu Baole

Discharge Summary:

The patient is a 56-year-old male; he was presented with polydipsia, polyphagia, and urorrhagia for the past 10 years, accompanied with edema in both lower limbs for the past 5 years. He has had hypertension for 5 years, the highest blood pressure reading reached 170/90mmHg. He took oral medication regularly, and the blood pressure was brought under control, at about 130/80mmHg. He had a coronary heart disease for the past 3 years, and took oral nitrates regularly. He has no chest distress or chest pain. He received a gall-stone operation to excise the gallbladder. He has no history of infectious diseases such as hepatitis or tuberculosis. The initial symptoms included thirst, polyuria and weight loss. He visited the local hospital and was diagnosed with diabetes. He took oral medication for treatment, but his blood sugar level was not brought under control. He was presented with edema in both lower limbs 5 years ago, and had numbness in both lower limbs. After regulating the oral hypoglycemic agents, the blood sugar level was still high. The extremities of the four limbs were presented with cyanosis 2 years ago. He felt sensations of heat and achiness after walking. The symptoms were aggravated, and he was started on insulin treatment. The numbness in both lower limbs was aggravated for a half a year. The blood sugar levels fluctuated between 12-18mmol/L. He eventually came to our hospital for further treatment.

Admission PE:

Bp: 157/76mmHg, Hr:75/min, fat. The patient was alert, and his spirits were good. He had good speech articulation. His memory, calculation abilities and orientation were normal. The respiration in both lungs was clear, the cardiac rhythm was regular. There was no diastolic murmur detected with the pulmonary valve auscultation. The abdomen was soft and there was no pain when pressed. There were no masses found. The pigmentation in both lower limbs was obvious, with moderate concavity edema. The muscle strength of all four limbs was level 5, the muscle tone of all four limbs was normal. The tendon reflexes of both upper limbs were normal; the tendon reflexes of both lower limbs were weak. The bilateral pathologic reflex was negative, the bilateral sensation was normal. The bilateral coordinated movements were normal. There were no signs of meningeal irritation.

Admission: FBG: 14.55mmol/L, PBG: 18.88mmol/L. After proper treatment, the blood sugar level was under control. RBG: 15.6mmol/L, Urine routine urine sugar (+++ ), acetone body (+), OGTT: FBG 12.59mmol/L. 2 hours later, the blood sugar level: 16.93mmol/L; glycolated hemoglobin: 12.5 %. ECG: sinus rhythm, V2-V4 lead T wave was harmonic average. Ultrasonic cardiogram: the left ventricular wall was fleshy; the motion of the left ventricular posterior regional wall was abnormal. LEVF 57%.

Ultrasound: mild fatty liver, the ultrasound of the carotid artery was consistent with the pathological changes of atherosclerosis. The nerve Electrophysiology was consistent with Diabetic Neuropathy (mild). He was 11% over normal bodyweight, has typical "polydipsia, polyphagia, and urorrhagia and weight loss " symptom. With the laboratory tests and examination results, he was diagnosed with diabetes type 2, Diabetic Neuropathy, hypertension level 3 (very high risk), coronary heart disease, fatty liver (mild).

Treatment Procedure:

The patient received health education regarding diabetes. He also received information on proper nutrition and advice on proper exercises. At the same time, we transplanted Mesenchymal Stem Cells and neural stem cells through the use of an I.V. The stem cells were transplanted each week for a total of 2 times. We also gave the patient oral medication and intravenous drugs to control the disease, and maintain normal blood sugar levels. We adjusted the stem cells in vivo, which allowed them to survive and perform the proper physiological actions.

Treatment Results:

The patient was in the hospital for 21 days, after potassium supplements, regulation of the blood sugar levels and correction of the acetone body (-), blood potassium rose to a normal level. Admission: The patient used insulin for treatment, the highest dosage was 75U. At present, the insulin treatment has been stopped and he only takes oral hypoglycemic agents. The blood sugar level is between 5.4 -7.2mmol/L, and has been controlled: The patient will be making follow-up visits for half a year.

The patient will continue to maintain a proper diet, and will exercise to control his blood sugar levels. His weight has been maintained at 70Kg (standard body weight). At present, the emphasis is on controlling the types of food he eats and on taking the oral medication for treatment. The blood sugar level while he is on an empty stomach is 5.6mmol/l, after meals is 6 - 8mmol/l.

Case Analysis:

Diabetes is one kind of chronic body-wide immunity metabolic disease. There are two kinds of clinical diabetes, type 1 and type 2. The onset of the disease is related to heredity, autoimmunity and environmental factors.

The statistics from WHO IN 2008: The rate of people who suffer from diabetes has increased from 3.4%, 5 years ago to 10% in 2008 (Chinese living in America is 20%), among them 90 - 95% are type 2 diabetics.

1. Inherited genetic factors

World wide recognition: diabetes is a hereditary disease; the genetic research indicates that the incidence rate of diabetes has a remarkable difference between blood relatives and non-blood relatives. The former case is 5 times higher than the latter case. With diabetes type 1, the hereditary factor's relevance is 50%, but with diabetes type 2, the hereditary factor's relevance reaches above 90%, therefore, the hereditary factors which cause diabetes type 2 are more significant than with diabetes type1.

2. Mental factors

Research within recent decades has confirmed the role of mental factors in the occurrence and development of diabetes, and is thought to be related to an increase in the amount of secretion of growth hormones, norepinephrine, adrenal hormones, etc., brought on by increased levels of mental stress.

3. The obesity factor

Recently, it is thought that obesity is an important contributing factor; about 60-80% of adult diabetics were overweight before the onset of the disease. The extent of the obesity has a positive relationship with the morbidity of the diabetes. The basal research material indicates: the rate of muscles and lipids changes with the development of age and the reduction of physical activities gradually.

4. Hyperphagia in the long-term

If the patient has out of control hyperphagia, this could cause the insulin B cells to have decreased or inadequate functioning, causing the insulin producing cells to have to work harder, potentially leading to diabetes. It is now understood that factors such as improper eating habits and obesity are directly linked to the increased possibility of developing diabetes.

5. Infections

There is a remarkable relationship between Juvenile diabetes and a virus infection, the infection will not cause diabetes by itself, meaning the diabetes exists, but the symptoms are not showing or the diabetes has not been diagnosed yet.

6. Pregnancy

It has been discovered that the number of times a woman has been pregnant has a positive correlation with the increased risks of developing diabetes. Multiple pregnancies will increase the genetic factors causing diabetes.

7. Specific genetic factors

It is now thought that diabetes is caused by a few specific damaged genes: type 1 diabetes-the HLA-D gene located in the 6th short arm chromosome is damaged; type II diabetes-insulin gene, insulin receptor, glucose lyase gene and mitochondria gene are damaged. Briefly, no matter which kind of diabetes, environmental factors, or virus infections, in the final analysis, the source of the disease is related to the damage to specific genes. In other words, diabetes is a genetic disease.

Recently, the advancement of the related research and gradual deeper understanding of the causes of diabetes can be attributed to the combination of the knowledge of molecular biology, use of the electron microscope ultrastructure, immunology, physiology and biochemistry, etc.; this has produced a deeper cognition of the pathogenesis of the disease.

The main causes for the development of type II diabetes are insulin resistance and insulin paracrisis, which are based on the damage to the autoimmunity Bcells and gene defects. Most of the researchers think that the insulin resistance is caused by the primary abnormality, but it is believed that it is very possible these two causes can exist at the same time, while the only differences are in the expression and the effectiveness of these causes.

Comprehensively, the mechanism of the type II diabetic's blood glucose increased exists in 2 aspects dysbolism:

1. The abnormality of the pancreas B cells, even the large reduction of the B cells (which is related with glucose or glycolipid toxicity) causes insulin paracrisis, insulin hyposecretion.

2. The tissues which are sensitive to insulin, such as found in the liver, and muscles, can lead to insulin resistance.

In the biomedical field, it has been confirmed that stem cells are a kind of multiple differentiation potential cell, acting like "seeds", which (the autologous stem cells with a defined quantity) are implanted into the tissue of the pancreas, "the seeds" can be guided to differentiate and proliferate into insulin producing cells, replace the damaged insulin B cells and secrete the insulin in the microenvironment of the pancreatic tissue. It overcomes to major problems: 1) The cells of the donor organs are in short supply; 2) Immunological rejection, the safety is remarkably increased. The literature from various nations all demonstrate that the curative effects of the stem cell implantation procedure is obvious in a short period of time, and the desired results of halting or decreasing the need of diabetic medication, as well as the safety of the procedure is good, with no obvious complications or discomfort to the patient.

The roles of treating diabetes by the use of stem cells:

1. Replacing the function of the abnormal B cells, increasing the quantity of the cells, restoring the autologous B cells, increasing the sensibility of the B cells to insulin, making insulin secretion more stable, and correcting insulin paracrisis.

2. Stem cells can repair the insulin postreceptor defects; the gene expression of the implanted stem cells will be normal, which can produce multiple normal working proteins, so there will be a decrease in the effects of insulin resistant proteins.

3. Stem cells can secrete plenty of insulin-like growth factor, to protect the pancreas.

4. Mesenchymal stem cells have the function of immunoregulation, which can treat the immune attacks to the tissue and organs. The expression of the stem cell functioning will be applied and exerted thoroughly under the control of experienced clinical doctors.

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